The events of the Great Crusade before the recovery of Horus are pretty vague, with several notable exceptions. As a result it's pretty much an open license for anyone to do anything. Hence, i'm making it canon (well fanon) that the Imperium's xenophobia is a result of, as you said, every encountered alien race being suicidally hostile.
And yes, the over-the-topedness of the regular sci-fantasy WTwU universe flows seamlessly with the over-the-topedness of 40k. It's perfect.
And HERE'S what that picture on the Imperial Fists (not Angry Marines) ship was of.
And enough text. Comic 543 nao!
Questions? Comments? Critique?